Exercise induces changes in somatotopic maps of the somatosensory or motor cortices of animals with brain or peripheral nerve injuries and these changes are related to functional recovery. In the case of spinal cord injury (SCI), exercise also improves recovery, but the effect of exercise on cortical organization after SCI is not well understood. The effect of SCI alone on cortical organization is well studied and SCI can alter somatotopic maps in two ways. The first is sometimes referred to as "silencing". This refers to the case when the region of the somatosensory cortex most affected by the injury does not respond to any cutaneous stimulation. The second possibility is that the affected region develops a novel somatotopic organization, such that the cells in this region respond to stimulation of peripheral areas innervated from spinal segments rostral to the injury. Cortical plasticity after spinal cord injury is likely to aid in learning novel sensorimotor strategies to maximize recovery. However, the effect of exercise on cortical organization after spinal cord injury is rarely addressed. Therefore, the relationship between changes in cortical organization and functional recovery after SCI remains unclear. The goal of this proposal is to determine if the cortical reorganization induced in response to therapeutic interventions after SCI contributes to improved functional recovery. To determine this, we will identify the relationship between cortical reorganization and functional recovery. Our central hypothesis is that reorganization of neuronal circuits in the cortex after mid-thoracic transection is necessary for functional recovery. Our preliminary data suggest that rats with mid-thoracic transection that receive therapeutic interventions to improve functional recovery demonstrate novel cortical organization in the brain such that deafferentated regions of the cortex are no longer silent after the spinalization. Moreover, in neonatally spinalized rats that achieve weight supported stepping, the novel cortical organization is correlated with functional recovery. We suggest, therefore, that reorganization of the cortex may play an important role in functional recovery. Our central hypothesis will be tested using two Specific Aims: Aim 1 Evaluate the role of reorganization in the sensorimotor cortex on the functional recovery of spinalized rats that receive exercise as a therapeutic intervention. Aim 2 Evaluate the role of reorganization in the sensorimotor cortex on the functional recovery of spinalized rats that receive exercise combined with serotonergic pharmacotherapy. PUBLIC HEALTH RELEVANCE: Brain reorganization after spinal cord injury Spinal cord injury affects more than 200,000 individuals in the United States and approximately 10,000 more patients sustain spinal cord injuries each year. When a person receives an SCI, the communication between the brain and other parts of the body is disrupted, and messages no longer flow past the damaged area. The goal of this project is to understand plasticity in the brain so that after injury, the brain can reorganize to improve function in patients.